Fig. 4: Hepatocyte-specific inhibition of IL11 cis-signaling protects mice against HFMCD diet-induced NASH.
a Schematic of HFMCD feeding regimen for AAV8-Alb-Cre injected Il11ra1loxP/loxP (conditional knockout; CKO) mice for experiments shown in (b–k). Il11ra1loxP/loxP mice were intravenously injected with either AAV8-Alb-Null or AAV8-Alb-Cre to delete Il11ra1 specifically in hepatocytes 3 weeks prior to the start of HFMCD diet. b Western blots of hepatic IL11RA and GAPDH (n = 3 mice/group). c Body weight (shown as a percentage (%) of initial body weight). d Representative gross anatomy, H&E-stained (scale bars, 50 µm), and Masson’s Trichrome (scale bars, 100 µm) images of livers. Representative dataset from n = 5 mice/group is shown for gross anatomy; representative dataset from n = 4 mice/group is shown for H&E-stained and Masson’s Trichrome images. e Hepatic triglycerides content. f Serum ALT levels. g Serum AST levels. h Hepatic GSH content. i Hepatic collagen levels. j Heatmap showing hepatic mRNA expression of pro-inflammatory markers (Tnfα, Ccl2, Ccl5) and fibrotic markers (Col1a1, Col1a2, Col3a1, Acta2). Values are shown in Supplementary Fig. 8c and d. k Western blots showing hepatic ERK and JNK activation status (n = 3 mice/group). c, e–j NCD (n = 5 mice/group), HFMCD (n = 6 mice/group). c Data are shown as mean ± SD, two-way ANOVA with Tukey’s correction, statistical significance (P values) are shown for comparison between WT HFMCD and CKO HFMCD; e–i data are shown as box-and-whisker with median (middle line), 25th–75th percentiles (box), and min–max values (whiskers); two-way ANOVA with Tukey’s correction. Source data are provided as a Source data file.
